Lnc027912 Reduces Lipid Accumulation Through Akt/MTOR/SREBP1C Axis in Hepatic Cells

Background: Various metabolism diseases are closely related to lipid metabolism disorder, but long noncoding-RNAs (lncRNA) involve in regulating function of lipid was limited elucidated. Previous our work have found that lnc027912 involve in cholesterol metabolism. Here, we further explore the role of lipid metabolism-associated lncRNA-lnc027912 in oleic acid- (OA) and palmitic acid (PA)-induced hepatic cells. Methods: The overexpression of lnc027912 cell model was constructed by using virus particles transfection, and the level of lnc027912 in AML12 cells were detected by RT-qPCR. High fat cell model was established by treating AML12 cells with OA and PA, and the level of lipid drops was detected by Oil red O staining and triglyceride analyze Kit. The lipid metabolism related-genes, such as SREBP1C, FAS, PPARγ, MTTP, ApoE and ApoC3 level, was detected using RT-qPCR and Western blot. The role of SREBP1C in lipid metabolism was further analyzed using double luciferase reporter gene assay and Immunofluorescence. The Akt/mTOR signal pathway related genes was detected by Western blot. Results: We found that TG level was inhibited in overexpression of lnc027912 cell. Upregulated lnc027912 of AML12 cells treated with OA and PA showed a significant decrease in lipid accumulation and TG levels. Furthermore, overexpression of lnc027912, the lipid biosynthesis genes of SREBP1C, FAS and PPARγ was significantly decreased and a significant increase in expression of MTTP and ApoE. Interestingly, lnc027912 inhibited Akt/mTOR signaling axis and decreased SREBP1C transit into nucleus and the promoter activity of SREBP1C and regulated expression of its targets. Conclusions: Our study revealed a new insights into the molecular function of lnc027912 in lipid metabolism by Akt/mTOR/SREBP1C signaling axis and highlights the potential of lnc027912 as a new therapeutic target for lipid disorder diseases (such as, NAFLD).